Results from this project will define some of the basic mechanisms involved in viral infection of mouse thymic cells using leukemic transformation of these cells as an end point. This is being done to better understand how known oncogenic viruses produce leukemia. An in vivo system for this study has been chosen in order to make the results more meaningful in understanding the actual viral induction of a malignant disease in an animal. Thymic grafts are exposed in vitro to various metabolic inhibitors at the time of 1) initial viral infection; 2) 24 hrs and 3 week established viral infection, and are placed under the kidney capsule in syngeneic hosts. Grafts are observed over a 180 day period for lymphoma development. To date we have found that inhibitors of RNA dependent DNA synthesis (reverse transcriptase) and DNA dependent DNA synthesis, both functions of viral enzymes as well as inhibitors of transcription, can prevent lymphomagenesis in grafts exposed to them at the time of initial viral infection. Three hour exposure to these inhibitors does not prevent lymphomagenesis with established viral infection in the thymic grafts.